Feasibility of pevonedistat combined with azacitidine, fludarabine, cytarabine in pediatric relapsed/refractory AML: Results from COG ADVL1712.

ABSTRACT:

Background

Outcomes for children with relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are poor, and new therapies are needed. Pevonedistat is an inhibitor of the NEDD-8 activating enzyme, a key regulator of the ubiquitin proteasome system that is responsible for protein turnover, with protein degradation regulating cell growth and survival.

Procedure

We evaluated the feasibility, toxicity, and pharmacokinetics (PK) of pevonedistat (20 mg/m² days 1, 3, 5) in combination with azacitidine, fludarabine, cytarabine (aza-FLA) in children with R/R AML and MDS (NCT03813147). Twelve patients were enrolled, median age was 13 years (range 1-21). Median number of prior chemotherapeutic regimens was two (range one to five), and two (25

SUBMITTER: Tarlock K 

PROVIDER: S-EPMC10864008 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature